Circulating tumor cells (CTCs) have important applications in clinical practice on early tumor diagnosis, prognostic prediction, and treatment evaluation. Platinum-based chemotherapy is a fundamental ...treatment for non-small cell lung cancer (NSCLC) patients who are not suitable for targeted drug therapies. However, most patients progressed after a period of treatment. Therefore, revealing the genetic information contributing to drug resistance and tumor metastasis in CTCs is valuable for treatment adjustment. In this study, we enrolled nine NSCLC patients with platinum-based chemotherapy resistance. For each patient, 10 CTCs were isolated when progression occurred to perform single cell–level whole-exome sequencing (WES). Meanwhile the patients’ paired primary-diagnosed formalin-fixed and paraffin-embedded samples and progressive biopsy specimens were also selected to perform WES. Comparisons of distinct mutation profiles between primary and progressive specimens as well as CTCs reflected different evolutionary mechanisms between CTC and lymph node metastasis, embodied in a higher proportion of mutations in CTCs shared with paired progressive lung tumor and hydrothorax specimens (4.4–33.3%) than with progressive lymphatic node samples (0.6–11.8%). Functional annotation showed that CTCs not only harbored cancer-driver gene mutations, including frequent mutations of
EGFR
and
TP53
shared with primary and/or progressive tumors, but also particularly harbored cell cycle–regulated or stem cell–related gene mutations, including
SHKBP1
,
NUMA1
,
ZNF143
,
MUC16
,
ORC1
,
PON1
,
PELP1
, etc., most of which derived from primary tumor samples and played crucial roles in chemo-drug resistance and metastasis for NSCLCs. Thus, detection of genetic information in CTCs is a feasible strategy for studying drug resistance and discovering new drug targets when progressive tumor specimens were unavailable.
The current study examined the change in local government staff's emotional distress over 7 years after the 2008 Wenchuan earthquake, and the influence of earthquake exposure and professional quality ...of life (ProQOL) on emotional distress.
This longitudinal study assessed 250 participants at 1 year after the earthquake; 162 (64.8%) were followed up at 7 years. Emotional distress was assessed with the Self-Reporting Questionnaire (SRQ) at both time points. We assessed ProQOL, including compassion satisfaction, burnout, and secondary traumatic stress, and earthquake exposure at 1 year. Wilcoxon signed-rank tests were performed to test longitudinal changes in emotional distress. Hierarchical multiple regression was conducted to examine the effect of earthquake exposure and ProQOL.
The positive screening rate of emotional distress (SRQ ≥ 8) was 37.6 and 15.4% at one and 7 years, respectively. Emotional distress scores declined over time (p < 0.001). Earthquake exposure and ProQOL predicted one-year (ps < 0.05) but not seven-year emotional distress, whereas burnout predicted both one-year (p = 0.018) and seven-year (p = 0.047) emotional distress.
Although emotional distress can recover over time, it persists even 7 years later. Actions to reduce burnout during the early stage of post-disaster rescue have long-term benefits to staff's psychological outcomes.
•Local government staff are crucial in post-disaster work but were under-studied.•The longitudinal study innovatively shows changes in PTSD and burnout over 7 years.•It was a first attempt to test ...reciprocal relationship between burnout and PTSD.
Although local government staff are crucial in post-quake reconstruction, their long-term psychological and professional consequences remain unclear. This longitudinal study investigated changes of posttraumatic stress disorder (PTSD) and professional burnout over seven years, and their underlying relationship. The study assessed 250 staff at one year (T1y) after the earthquake, and 162 (64.8 %) were followed up at seven years (T7y). PTSD and professional burnout were assessed with the Short Screening Scale for DSM-IV PTSD and the burnout subscale of Professional Quality of Life Scale (ProQOL), respectively, at both time points. Longitudinal changes in PTSD and burnout were examined and cross-lagged panel analyses were conducted to test the relationship between PTSD and burnout. The rates of positive cases of PTSD screening were 23.2 % at T1y and 11.1 % at T7y. The percentages of moderate burnout were 61.7 % at T1y and 23.5 % at T7y. Scores of PTSD (z = -5.70, p < 0.001) and burnout (t = 10.07, p < 0.001) from T1y to T7y decreased. The cross-lagged analysis indicated that burnout at T1y predicted PTSD at T7y (β = 0.19, p = 0.025). In conclusion, the Wenchuan earthquake has long-lasting negative effects on local government staff, although they can recover over time. Interventions to reduce professional burnout after disaster may does be beneficial to decrease the risk of PTSD in the long run.
Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to ...characterize IM subtypes and investigate potential mechanisms in LMs.
Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort. Transcriptomic and whole-exome sequencing were used to explore potential mechanisms across distinct IM subtypes. Single-cell transcriptomic sequencing, multiplex fluorescent immunohistochemistry, cell culture, mouse model, Western blot, quantitative polymerase chain reaction, and immunohistochemistry were used for validation.
Five IM subtypes were revealed in 100 LMs and 50 primary liver cancers. Patients featured terminally exhausted (IM1) or rare T-cell-inflamed (IM2 and IM3) immune characteristics showed worse outcome. Increased intratumor heterogeneity, enriched somatic TP53, KRAS, APC, and PIK3CA mutations and hyperactivated hypoxia signaling accounted for the formation of vicious subtypes. SLC2A1 promoted immune suppression and desert via increasing proportion of Spp1+ macrophages and their inhibitory interactions with T cells in liver metastatic lesions. Furthermore, SLC2A1 promoted immune escape and LM through inducing regulatory T cells, including regulatory T cells and LAG3+CD4+ T cells in primary colorectal cancer.
The study provided integrated multi-omics landscape of LM, uncovering potential mechanisms for vicious IM subtypes and confirming the roles of SLC2A1 in regulating tumor microenvironment remodeling in both primary tumor and LM lesions.
▪
Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China
. However, whole-genome analysis of hepatitis B virus (HBV)-associated HCC in Chinese individuals is limited
, with ...current analyses of HCC mainly from non-HBV-enriched populations
. Here we initiated the Chinese Liver Cancer Atlas (CLCA) project and performed deep whole-genome sequencing (average depth, 120×) of 494 HCC tumours. We identified 6 coding and 28 non-coding previously undescribed driver candidates. Five previously undescribed mutational signatures were found, including aristolochic-acid-associated indel and doublet base signatures, and a single-base-substitution signature that we termed SBS_H8. Pentanucleotide context analysis and experimental validation confirmed that SBS_H8 was distinct to the aristolochic-acid-associated SBS22. Notably, HBV integrations could take the form of extrachromosomal circular DNA, resulting in elevated copy numbers and gene expression. Our high-depth data also enabled us to characterize subclonal clustered alterations, including chromothripsis, chromoplexy and kataegis, suggesting that these catastrophic events could also occur in late stages of hepatocarcinogenesis. Pathway analysis of all classes of alterations further linked non-coding mutations to dysregulation of liver metabolism. Finally, we performed in vitro and in vivo assays to show that fibrinogen alpha chain (FGA), determined as both a candidate coding and non-coding driver, regulates HCC progression and metastasis. Our CLCA study depicts a detailed genomic landscape and evolutionary history of HCC in Chinese individuals, providing important clinical implications.
•Probiotic supplementation enhances cognitive functions in MCI older adults.•Probiotic supplementation benefits sleep quality in MCI older adults.•Probiotic supplementation increases the abundance of ...intestinal flora.
Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI.
Stage I non-small cell lung cancer (NSCLC) presents diverse outcomes. To identify molecular features leading to tumor recurrence in early-stage NSCLC, we perform multiregional whole-exome sequencing ...(WES), RNA sequencing, and plasma-targeted circulating tumor DNA (ctDNA) detection analysis between recurrent and recurrent-free stage I NSCLC patients (CHN-P cohort) who had undergone R0 resection with a median 5-year follow-up time. Integrated analysis indicates that the multidimensional clinical and genomic model can stratify the prognosis of stage I NSCLC in both CHN-P and EUR-T cohorts and correlates with positive pre-surgical deep next generation sequencing (NGS) ctDNA detection. Increased genomic instability related to DNA interstrand crosslinks and double-strand break repair processes is significantly associated with early tumor relapse. This study reveals important molecular insights into stage I NSCLC and may inform clinical postoperative treatment and follow-up strategies.
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•Multi-sequencing with recurrent timing provides deep insights into early-stage NSCLC•Asian NSCLCs exhibit diverse genomic features•Integrative analysis can stratify stage I NSCLC prognosis, verified by ctDNA•Dysfunction of DNA ICL-DSB events inducing GI contributes to early tumor recurrence
Chen et al. describe genomic features that differ between Asian and Caucasian NSCLC and molecular features of early-relapse stage I NSCLC based on multiregional tumor sequencing and relapse-timing analysis. They develop an integrative clinical-genomic factor model stratifying stage I NSCLC prognosis and extend genomic insights into early-stage NSCLC.
To analyse the reason and countermeasure for the infection of severe acute respiratory syndrome (SARS) in health care workers, to provide reference for the health care workers to control infection of ...SARS.
To analyse retrospectively the reason and countermeasure 19 infective cases of SARS among the health care workers in our hospital from 16th March, 2003 to 3rd May, 2003.
Except for 4 fellow-doctors were infected by close contact in a same dormitory, all others were infected on work-station of close contact with SARS patients, there were no more cross-infection among the health care workers.
It is important to improve the protection even for the health care workers without contact of SARS patients, and it's necessary to wear mask, goggles, and gloves, health care workers with contact with SARS patients must be separated according the extent of contact separately, and draw guideline in advance.
Tuberculosis remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent. Despite chemotherapy, the global tuberculosis epidemic has intensified ...because of HIV co-infection, the lack of an effective vaccine and the emergence of multi-drug-resistant bacteria. Alternative host-directed strategies could be exploited to improve treatment efficacy and outcome, contain drug-resistant strains and reduce disease severity and mortality. The innate inflammatory response elicited by Mycobacterium tuberculosis (Mtb) represents a logical host target. Here we demonstrate that interleukin-1 (IL-1) confers host resistance through the induction of eicosanoids that limit excessive type I interferon (IFN) production and foster bacterial containment. We further show that, in infected mice and patients, reduced IL-1 responses and/or excessive type I IFN induction are linked to an eicosanoid imbalance associated with disease exacerbation. Host-directed immunotherapy with clinically approved drugs that augment prostaglandin E2 levels in these settings prevented acute mortality of Mtb-infected mice. Thus, IL-1 and type I IFNs represent two major counter-regulatory classes of inflammatory cytokines that control the outcome of Mtb infection and are functionally linked via eicosanoids. Our findings establish proof of concept for host-directed treatment strategies that manipulate the host eicosanoid network and represent feasible alternatives to conventional chemotherapy.
In hyperspectral image (HSI) classification, convolutional neural networks (CNNs) and transformer architectures have each contributed to considerable advancements. CNNs possess potent local feature ...representation skills, whereas transformers excel in learning global features, offering a complementary strength. Nevertheless, both architectures are limited by static receptive fields, which hinder their accuracy in delineating subtle boundary discrepancies. To mitigate the identified limitations, we introduce a novel dual-branch adaptive convolutional transformer (DBACT) network architecture featuring an adaptive multi-head self-attention mechanism. The architecture begins with a triadic parallel stem structure for shallow feature extraction and reduction of the spectral dimension. A global branch with adaptive receptive fields performs high-level global feature extraction. Simultaneously, a local branch with a cross-attention module provides detailed local insights, enriching the global perspective. This methodical integration synergizes the advantages of both branches, capturing representative spatial-spectral features from HSI. Comprehensive evaluation across three benchmark datasets reveals that the DBACT model exhibits superior classification performance compared to leading-edge models.
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